The aimes of this proposal are threefold: (1) To define and characterize the suppressor lymphoid cells which appear during tumor growth. What are they? When do they arise? Are they specific? Are they irreversibly precomitted? Can they be purified? How do they exert their suppressor effect? What is the fate of cells exposed to their influence? How can their effect be mimimized by elimination of selected populations by appropriate drugs? (2) To study the effects on suppressor functions of two immunotherapy systems--active specific immunotherapy with neuraminidase treated tumor cells and adoptive immunotherapy with lymphoid cells sensitized in vitro to syngeneic tumor antigens. (3) To study how elimination of suppressor function by drug treatment can interact with improved immunotherapy protocols to shift the immunologic balance in favor of host survival. In vitro techniques of two general types will be utilized: (a) Assay for various functional subpopulations of lymphoid cells from normal and tumor and bearing hosts under defined conditions of drug treatment and immunotherapy. (b) Techniques to improve the immunity derived from exposure of syngeneic tumor cells to responsive lymphoid cells.